Antibiotic resistant infections are a global clinical and public health problem that has emerged with alarming rapidity in recent years and undoubtedly will increase in the near future. For example, bacterial infections caused by methicillin-resistant Staphylococci, such as methicillin-resistant Staphylococcus aureus (MRSA), are increasing in prevalence in both the hospital and community settings. Staphylococci are found on the skin and within the digestive and respiratory tracts but can infect open wounds and burns and can progress to serious systemic infection. The emergence of multi-drug resistant Staphylococci, especially, in the hospital where antibiotic use is frequent and this selective pressure for drug-resistant organism is high, has proven a challenge for treating these patients. The presence of MRSA on the skin of patients and health care workers has promoted transmission of multi-drug resistant organisms in health care settings.
Likewise, other antibiotic resistant bacteria, such as ciprofloxacin-resistant, and/or vancomycin-resistant strains are making current treatments less effective in combating infections arising from these microorganisms. And because drug resistant micro-organisms is a growing problem, the morbidity, mortality, and financial costs of such infections pose an increasing burden for health care systems worldwide. Strategies to address these issues emphasize enhanced surveillance of resistance, increased monitoring and improved usage of antimicrobial drugs, professional and public education, development of new drugs, and assessment of alternative therapeutic modalities. Accordingly, there is a need in the art for additional therapies for treating and preventing a bacterial infection.
Additionally, there is a need in the art for cancer therapeutic agents. Cancer is characterized by unrestricted cell growth and many cancer therapies work by inhibiting cell division. Although new therapeutics focus on inhibiting cell division because normal cells do not divide after maturation, normal cells are nevertheless affected by antitumor agents. And there is tremendous variability in the efficacy of certain chemotherapeutic agents; some drugs are more effective than others for certain patients, for certain cancers, or at certain stages of treatment.
Continuing, inflammation comes as the immune system's first response to infection or irritation. Inflammatory diseases are typically characterized by one or more of the following symptoms: redness, swollen joints warm to the touch, joint pain, joint stiffness, and loss of joint function. While several treatments are currently available to decrease joint pain, swelling and inflammation, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (e.g., prednisone), anti-malarial agents (e.g., hydroxychloroquine), and acetaminophen, their strong side effects often limit their use.
In fact, autoimmune diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, glomerulonephritis, inflammatory bowel diseases (Morbus Cohn, colitis ulcerosa), psoriasis) are among the major health problems worldwide. Autoimmune diseases are among the ten leading causes of death. Most of autoimmune diseases require lifelong treatment (Jacobson D L, Gange S J, Rose N R, Graham N M. Clin Immunol Immunopathol 1997; 84:223-43). The standard of care for treating many autoimmune diseases includes a regimen containing anti-inflammatory agents.
Accordingly, because the effective treatment of many diseases and disorders remains a challenge in modern medicine, there is also a need in the art for additional agents for treating cancer and autoimmune and inflammatory conditions. The present invention satisfies that need.
The inventors of the present invention surprisingly found that silicate itself is useful in treating a number of conditions. While Gibson et al. previously reported that the bioactivity of hydroxyapatite is enhanced by the incorporation of silicate ions into a hydroxyapatite lattice, Gibson did not recognize the therapeutic value of silicate alone, or the use of silicate in treating a number of other conditions, including bacterial infections and cancer. See, for example, Gibson et al., Key Eng. Mater. 218-220 (2002) 203-206.
Furthermore, Bensal HP (containing salicylic acid, benzoic acid, PEG and QRB-7 (red oak bark extract)) is being sold for use in complications associated with pyodermas, and Lexaderm (containing salicylic acid, benzoic acid, and QRB-7) is being sold as an anti-bacterial, anti-fungal, anti-inflammatory ointment for veterinary use. These compositions, however, do not contain silicate alone and it would not have been possible to identify silicate as an active ingredient in these compositions based on reverse engineering Bensal HP, Lexaderm, or QRB-7, or any of the individual elements in these compositions.
U.S. Pat. Nos. 5,658,896 and 5,534,509 disclose the use of silicate polymers that may be used to treat certain diseases but do not disclose silicate containing compositions that are not polymerized or their use in treating cancer.